摘要:

Abstract:Determinants of host—drug interaction comprise a complex of potentially variable factors. The complexity of this variability compromises the forecasting of favorable response in individual patients given standard therapy. Substantial success with current forms of chemotherapy may require that biochemical, pharmacologic, and clinical profiles be established for each cancer patient whereby the use of drug and drug combination can be rationally applied. The significance of evaluating clinical pharmacokinetic parameters in patients with cancer is placed in perspective with other factors relevant to individual drug respons

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02707.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The bronchodilator effect of fenoterol hydrobromide (0.5, 1.25, and 2.5 mg) was compared with either isoproternol (2.8 mg) or isoetharine (5 mg) with phenylephrine (1.25 mg) in a double‐blind placebo‐controlled study. When delivered by an intermittent positive‐pressure breathing device to 24 nonsmoking young adult asthmatic subjects, fenoterol produced significant improvement in forced expiratory volume at 1 second (FEV1), in maximum midexpiratory flow (FEF25–75%), and in forced expiratory flow at 25 per cent of vital capacity (FEF25%) for 6 to 8 hours, whereas isoproterenol and isoetharine with phenylephrine produced improvement for 1 and 2 hours, respectively. The lowest dosage of fenoterol was as effective as the highest but had fewer adverse

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02708.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Acute intravenous and short‐term oral mexiletine therapy was effective in suppressing the arrhythmia in six of eight patients with recurrent ventricular tachycardia. Five of the six patients who were placed on maintenance therapy remained asymptomatic during a mean follow‐up of 15 months. The study shows that the acute and short‐term suppression of ventricular tachycardia by mexiletine can be a useful predictor of its long‐term e

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02709.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The acute effects of intravenous nadolol (0.01 and 0.02 mg/kg) on cardiac electrophysiologic parameters were assessed with His bundle recording and programmed atrial stimulation. The higher dose of nadolol reduced resting heart rate (71 vs. 65 beats/min,P<0.02), and the degree of slowing was related to the initial heart rate (r = −0.68,P<0.05). Atrioventricular conduction time as defined by the paced A—H interval, rose by 12 msec (P<0.001) after nadolol (0.02 mg/kg) administration. Atrial refractoriness increased (by 10 msec,P<0.02) only at the higher dose level with nadolol. At both dose levels, atrioventricular nodal effective and functional refractory periods were increased (P<0.02) by a mean of 45 and 21 msec, respectively, suggesting greater sensitivity of atrioventricular nodal refractoriness to beta‐adrenergic blockade. Nadolol's effects were generally similar to those of previously reported studies with other beta‐adrenergic blockers. These data suggest that nadolol slows conduction through the atrioventricular node and increases atrial and atrioventricular nodal refract

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02710.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Severely anxious hospitalized patients were treated with rapidly increasing doses of two benzodiazepine compounds to test the feasibility of rapid pharmacotherapy of the condition. Twenty‐one subjects completing the study all obtained substantial relief from symptoms; in only three subjects were symptoms completely eliminated. No serious side effects were encountere

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02711.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Twenty infants and children receiving intravenous chloramphenicol were studied to examine the pharmacokinetics of the parent compound and its precursor, the succinate ester (CAP‐S). Plasma samples were obtained just prior to a 30‐minute infusion of chloramphenicol succinate, immediately after or 30 minutes after infusion, and 90, 210, and 330 minutes after infusion. Complete 6‐hour urine collections were obtained during 11 studies. Plasma and urine were assayed for chloramphenicol and its succinate ester by high‐performance liquid chromatography. Peak plasma concentrations ranged from 11.0 to 51.1 μg/ml on doses of 50 to 100 mg/kg/day and were higher in the youngest age group. The elimination half‐life of chloramphenicol averaged 4.0 hours. Multilinear regression analysis demonstrated an excellent relationship between body surface area, trough plasma chloramphenicol concentration, and total body chloramphenicol clearance. The hydrolysis of succinate ester to free chloramphenicol may delay the peak free concentration, and its renal elimination (average 21 per cent of the dose administered) significantly affects chloramphenicol pharmacokinetics. The clearance of chloramphenicol exhibited enzyme saturation kinetics in one patient studied at two different doses. Dosage adjustments of intravenous chloramphenicol in children must be made in relation to the trough chloramphenicol plasma concentration, renal elimination of CAP‐S, and possible saturation of chloramphenico

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02712.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Twelve patients having frequent premature ventricular complexes (PVCs) averaging more than 60 per hour received a single 150‐mg intravenous dose of pirmenol. Plasma pirmenol concentration declined biexponentially following the infusion and was analyzed according to a two‐compartment open model. Following an erratic distribution phase, the terminal elimination half‐life ranged from 4.2 to 16.9 hours, with a geometric mean of 7.6 hours. Total body clearance averaged 164 ± 58 ml/min, and the mean volume of distribution was 1.45 ± 0.38 liter/kg. Renal clearance averaged 46.6 ± 21.2 ml/min, representing 30 ± 10 per cent of total body clearance. Excretion of unchanged drug in the urine averaged 31.8 ± 8 per cent of the dose. Renal clearance and elimination half‐life were correlated (r= −0.61,P<0.05). Eight of the 12 patients achieved greater than 95 per cent suppression of PVCs with a duration between 20 minutes and 23 hours. These favorable pharmacokinetics indicate that pirmenol may be a useful addition to the therapy of ventricul

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02713.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Twenty patients received dipyridamole by two different dosage regimens yielding a total daily dose of 150 mg, either as 50 mg three times a day or 75 mg twice a day. The rationale for comparing these two regimens is that dipyridamole is usually given three times a day, but recent studies have revealed a final elimination half‐life of the drug of about half a day. Based on drug cumulation during chronic dosing, the final half‐life of dipyridamole observed in this study also averaged about half a day. The 75 mg b.i.d. regimen did not result in lower trough concentrations than the 50 mg t.i.d. regimen. There was wide interpatient variability in observed plasma dipyridamole concentrations for both regimens, averaging about 10‐fold. These results suggest that dipyridamole could be administered twice a day and that dipyridamole levels should be monitored in clinical studies on the antithrombotic effect of the

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02714.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY